c-JUN: a chromatin repressor that limits mesoderm differentiation in human pluripotent stem cells.

Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on chromatin loci to limit mesoderm cell fate specification as cells exit pluripotency. Although c-JUN is widely expressed across various cell types in early embryogenesis, it is not essential for maintaining pluripotency.

The role of BATF in immune cell differentiation and autoimmune diseases.

As a member of the Activator Protein-1 (AP-1) transcription factor family, the Basic Leucine Zipper Transcription Factor (BATF) mediates multiple biological functions of immune cells through its involvement in protein interactions and binding to DNA. Recent studies have demonstrated that BATF not only plays pivotal roles in innate and adaptive immune responses but also acts as a crucial factor in the differentiation and function of various immune cells. Lines of evidence indicate that BATF is associated with the onset and progression of allergic diseases, graft-versus-host disease, tumors, and autoimmune diseases.

Association between lactate dehydrogenase levels and all-cause mortality in ICU patients with heart failure: a retrospective analysis of the MIMIC-IV database.

Background: Heart failure (HF) patients admitted to the intensive care unit (ICU) often face high short-term mortality rates. This study aims to investigate the relationship between lactate dehydrogenase (LDH) levels and all-cause mortality in critically ill patients with HF.

Methods: Data from the MIMIC-IV database were extracted for subjects eligible for HF diagnosis.

Dual modality feature fused neural network integrating binding site information for drug target affinity prediction.

Accurately predicting binding affinities between drugs and targets is crucial for drug discovery but remains challenging due to the complexity of modeling interactions between small drug and large targets. This study proposes DMFF-DTA, a dual-modality neural network model integrates sequence and graph structure information from drugs and proteins for drug-target affinity prediction. The model introduces a binding site-focused graph construction approach to extract binding information, enabling more balanced and efficient modeling of drug-target interactions.

Robust mucosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish polyfunctional resident memory in patient lungs.

Mucosal antigen-specific T cells are pivotal for pathogen clearance and immune modulation in respiratory infections. Dysregulated T cell responses exacerbate coronavirus disease 2019 severity, marked by cytokine storms and respiratory failure. Despite extensive description in peripheral blood, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in the lungs remain elusive.

Symptom-based depression subtypes: brain dynamic specificity and its association with gene expression profiles.

At least 227 combinations of symptoms meet the criteria for Major Depressive Disorder (MDD). However, in clinical practice, patients consistently present symptoms in a regular rather than random manner, and the neural basis underlying the MDD subtypes remains unclear. To help clarify the neural basis, patients with MDD were clustered by symptom combinations to investigate the neural underpinning of each subtype using functional resonance imaging (fMRI).

Multiple token rearrangement Transformer network with explicit superpixel constraint for segmentation of echocardiography.

Diagnostic cardiologists have considerable clinical demand for precise segmentation of echocardiography to diagnose cardiovascular disease. The paradox is that manual segmentation of echocardiography is a time-consuming and operator-dependent task. Computer-aided segmentation can reduce the workflow greatly.

Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system.

Combining Multifrequency Magnetic Resonance Elastography With Automatic Segmentation to Assess Renal Function in Patients With Chronic Kidney Disease.

Background: Multifrequency MR elastography (mMRE) enables noninvasive quantification of renal stiffness in patients with chronic kidney disease (CKD). Manual segmentation of the kidneys on mMRE is time-consuming and prone to increased interobserver variability.

Purpose: To evaluate the performance of mMRE combined with automatic segmentation in assessing CKD severity.

Systematic analyses uncover robust salivary microbial signatures and host-microbiome perturbations in oral squamous cell carcinoma.

Unlabelled: Oral squamous cell carcinoma (OSCC) is a prevalent malignancy in the oral-maxillofacial region with a poor prognosis. Oral microbiomes play a potential role in the pathogenesis of this disease. However, findings from individual studies have been inconsistent, and a comprehensive understanding of OSCC-associated microbiome dysbiosis remains elusive.

CCN5 suppresses injury-induced vascular restenosis by inhibiting smooth muscle cell proliferation and facilitating endothelial repair via thymosin β4 and Cd9 pathway.

Background And Aims: Members of the CCN matricellular protein family are crucial in various biological processes. This study aimed to characterize vascular cell-specific effects of CCN5 on neointimal formation and its role in preventing in-stent restenosis (ISR) after percutaneous coronary intervention (PCI).

Methods: Stent-implanted porcine coronary artery RNA-seq and mouse injury-induced femoral artery neointima single-cell RNA sequencing were performed.

Skeletal organoids.

The skeletal system, composed of bones, muscles, joints, ligaments, and tendons, serves as the foundation for maintaining human posture, mobility, and overall biomechanical functionality. However, with ageing, chronic overuse, and acute injuries, conditions such as osteoarthritis, intervertebral disc degeneration, muscle atrophy, and ligament or tendon tears have become increasingly prevalent and pose serious clinical challenges. These disorders not only result in pain, functional loss, and a marked reduction in patients' quality of life but also impose substantial social and economic burdens.

Future perspectives: advances in bone/cartilage organoid technology and clinical potential.

Bone and cartilage tissues are essential for movement and structure, yet diseases like osteoarthritis affect millions. Traditional therapies have limitations, necessitating innovative approaches. Organoid technology, leveraging stem cells' regenerative potential, offers a novel platform for disease modelling and therapy.

Integration of single-cell transcriptome and chromatin accessibility and its application on tumor investigation.

The advent of single-cell sequencing techniques has not only revolutionized the investigation of biological processes but also significantly contributed to unraveling cellular heterogeneity at unprecedented levels. Among the various methods, single-cell transcriptome sequencing stands out as the best established, and has been employed in exploring many physiological and pathological activities. The recently developed single-cell epigenetic sequencing techniques, especially chromatin accessibility sequencing, have further deepened our understanding of gene regulatory networks.

4D live tracing reveals distinct movement trajectories of meiotic chromosomes.

Proper chromosome alignment at the spindle equator is a prerequisite for accurate chromosome segregation during cell division. However, the chromosome movement trajectories prior to alignment remain elusive. Here, we established a 4D imaging analysis framework to visualize chromosome dynamics and develop a deep-learning model for chromosome movement trajectory classification.

Fatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH.

Dyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls.

Danshen injection ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibiting ferroptosis via activating SIRT1/GPX4 pathway.

Introduction: The pathogenesis of renal fibrosis is related to blood stasis, and the method of promoting blood circulation and removing blood stasis is often used as the treatment principle. Danshen injection (DSI) is a commonly used drug for promoting blood circulation and removing blood stasis in clinic. However, whether DSI slows the progression of renal fibrosis or the potential mechanism is uncertain.

Identification of Epinastine as CD96/PVR inhibitor for cancer immunotherapy.

Background: Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor immune evasion. Therefore, screening of immune checkpoint inhibitors (ICIs) targeting the CD96/PVR pathway will provide promising candidates for tumor immunotherapy.

Safety and efficacy of tirofiban in the endovascular treatment of intracranial aneurysms: a systematic evaluation and meta-analysis.

Patients with intracranial aneurysms (IA) undergoing endovascular treatment face varying risks and benefits when tirofiban is used for thromboprophylaxis during surgery. Currently, there is a lack of high-level evidence summarizing this information. This study aims to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of tirofiban during endovascular treatment of IA.

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis.

Downregulation of HDAC2 attenuates ventricular arrhythmias in a mouse model of cardiac hypertrophy through upregulation of KCHIP2 expression.

Aims: Decrease in repolarizing K+ currents, particularly the fast component of transient outward K+ current (Ito,f), prolongs action potential duration (APD) and predisposes the heart to ventricular arrhythmia during cardiac hypertrophy. Histone deacetylases (HDACs) have been suggested to participate in the development of cardiac hypertrophy, and class I HDAC inhibition has been found to attenuate pathological remodeling. This study investigated the potential therapeutic effects of HDAC2 on ventricular arrhythmia in pressure overload-induced cardiac hypertrophy.

Glutamate-mediated antidepressant effects of Jieyu I Formula via modulation of PFC-LHb circuitry in lipopolysaccharide-induced depression model.

Ethnopharmacological Relevance: Jieyu I Formula (JY-I) is an improved version of the classic formula "Sini San" documented in the books Shanghan Lun, which is known for regulating the liver and treating depression. However, the disturbance of neuronal signal transmission in the neural circuit of the brain is closely related to the occurrence of depression, yet its neural mechanism is still unclear.

Aim Of The Study: This study aimed to observe the antidepressant effect of JY-I on depressed mice induced by lipopolysaccharide and its underlying central nervous system mechanisms, focusing on the prefrontal cortex (PFC) to lateral habenular nucleus (LHb) neural circuit in the depressed mice model.